Decrease In Firing Rate Research Articles

Effect of chronic lithium treatment on D 2/3 autoreceptor regulation of dopaminergic function in the rat

Dysregulation of mesolimbic dopamine (DA) neurotransmission has been implicated in bipolar disorder. DA release in the nucleus accumbens is reduced in rats treated chronically with the mood stabiliser lithium, and this effect is maintained for 3 days after withdrawal from the lithium treatment. We tested whether this decrease in DA release is due to an increase in D 2/3 autoreceptor sensitivity. In vivo microdialysis studies showed that in the shell of the nucleus accumbens, dialysate DA was decreased following chronic lithium treatment and 3 days after withdrawal from lithium treatment. The elevation of dialysate DA induced by local blockade of the terminal D 2/3 receptor was reduced in both lithium treated and lithium withdrawn groups. In vitro electrophysiology studies showed that chronic lithium treatment (and lithium withdrawal) did not alter either basal firing rate of DA neurones in the ventral tegmental area, or somatodendritic D 2/3 autoreceptor-mediated inhibition of firing. D 2 mRNA expression in the ventral tegmental area was unchanged by lithium treatment and lithium withdrawal. Our data suggest that the decrease in dopamine release in the nucleus accumbens induced by chronic lithium treatment is not the result of increased terminal or somatodendritic autoreceptor sensitivity or decreased firing rate of DA neurones.

Interleukin‐1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post‐synaptic potentials

In vitro electrophysiological data suggest that interleukin-1 may promote non-rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN). Interleukin-1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin-1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin-1beta. Coronal slices containing DRN were obtained from male Sprague-Dawley rats. The impact of interleukin-1 on firing rate and on evoked post-synaptic potentials was determined. Evoked post-synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin-1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 +/- 0.2 Hz (before administration) to 0.7 +/- 0.2 Hz. Electrical stimulation induced depolarizing evoked post-synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post-synaptic potential components: a GABAergic evoked inhibitory post-synaptic potentials and a glutamatergic evoked excitatory post-synaptic potentials, respectively. Interleukin-1 increased GABAergic evoked inhibitory post-synaptic potentials amplitudes by 30.3 +/- 3.8% (n = 6) without affecting glutamatergic evoked excitatory post-synaptic potentials. These results support the hypothesis that interleukin-1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin-1-induced potentiation of evoked GABAergic inhibitory responses.

Peroxynitrite donor impairs excitability of hippocampal CA1 neurons by inhibiting voltage-gated potassium currents

Nitric oxide (NO) reacts rapidly with superoxide anion and produces peroxynitrite (ONOO −), which is a highly reactive free radical that has been shown to mediate much of the toxicity of NO. ONOO − has also been implicated as playing a role in the pathology of various brain disorders. The aim of this study was to investigate the actions of ONOO − on voltage-activated potassium currents and its effect on membrane excitability in hippocampal CA1 neurons. SIN-1(3-morpholino-sydnonimine), which leads to the simultaneous generation of superoxide anion and NO, and then forms the highly reactive species ONOO −, induced a dose-dependent inhibition in amplitudes of transient potassium currents ( I A) and delayed rectifier potassium currents ( I K). SIN-1 (500 μM) produced a hyperpolarizing shift in the activation–voltage curve of both I A and I K and delayed the recovery of I A from inactivity, but did not have a marked effect on the inactivation parameters of I A. However, co-treatment with SIN-1 and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP, 100 μM), an ONOO − scavenger, had no effects on I A and I K currents. SIN-1 (500 μM) led to increase in action potential duration and decrease in action potential firing rate. The results suggest that changes of I A and I K currents induced by ONOO − in hippocampal neurons have influence on excitability of hippocampal CA1 neurons, which are related to its neurotoxicity.

Activation of rat ventral tegmental area dopamine neurons by endogenous kynurenic acid: A pharmacological analysis

Kynurenic acid (KYNA) is an endogenous NMDA receptor antagonist as well as a blocker of the α7* nicotinic receptor and mounting evidence suggests that the compound participates in the pathophysiology of schizophrenia. Previous studies have shown that elevated levels of endogenous KYNA are associated with an increased firing of midbrain dopamine (DA) neurons. In the present study, utilizing extracellular single unit cell recording techniques, the mechanism involved in this excitatory action of the compound was analyzed in male Sprague–Dawley rats. Administration of 4-chlorokynurenine (4-Cl-KYN; 25 mg/kg, i.p.), which is converted to the selective NMDA glycine-site antagonist 7-chloro-kynurenic acid (7-Cl-KYNA), was found to increase firing rate and per cent burst firing activity of ventral tegmental area (VTA) DA neurons to the same magnitude as pretreatment of kynurenine (causing a 25-fold elevation in extracellular brain KYNA). Intravenous administration of the selective antagonist at the α7* nicotinic receptor methyllycaconitine (MLA; 1–4 mg/kg) did not affect firing of VTA DA neurons, whereas intraperitoneal administration of this drug in a high dose (6 mg/kg) was associated with a decreased firing rate and per cent burst firing activity. Administration of SDZ 220-581 (10 mg/kg, i.v.), a competitive antagonist at the glutamate recognition-site of the NMDA receptor, was found to increase firing rate and per cent burst firing. Present results have potential implications for the treatment of schizophrenia, and indicate that the increased activity of VTA DA neurons following elevation of brain KYNA is mediated through glutamatergic rather than by nicotinergic mechanisms.

Factors affecting the turns analysis of the interference EMG signal

This study was performed to evaluate the relative significance of changes typical for muscle fatigue on quantitative parameters obtained from turns analysis of simulated intramuscular and surface interference electromyographic (EMG) signals. Effects of reduction of firing rate of motor units (MUs) and changes of intracellular action potential (IAP) profile along active fibers were analyzed. A new analytic function was proposed to simulate changes in IAP shape at different stages of muscle fatigue. In intramuscular EMG, both the decrease in firing rate of MUs and the changes in IAP profile led to reduction in the number of turns per second (NTs) and mean turn amplitude (MTA). The development of fatigue and especially the changes in IAP profile could explain why NTs increased up to only about 50% of maximal voluntary contraction, and remained unchanged above that level of efforts or even decreased. These effects should be especially pronounced in patients with myopathy whose IAP and muscle fatigability are expected to be abnormal. In surface EMG, the MTA increased considerably with fatigue; the sensitivity of NTs to reduction in firing rate (or number of discharges) was low. Thus, the benefits of the turns analysis of surface EMG signals should be lower not only in diagnosis of myopathy but also neuropathy.

Ryanodine receptor Ca2+‐release channels are an output pathway for the circadian clock in the rat suprachiasmatic nuclei

Ryanodine-sensitive intracellular Ca2+ channels (RyRs) are present in suprachiasmatic nuclei (SCN) neurons, but the functions served by these channels are not known. Here we addressed whether mobilization of intracellular Ca2+ stores through the RyRs may be a link between the molecular clock and the firing rate in SCN neurons. Activation of the RyRs by administration of either 1 mM caffeine or 100 nM ryanodine increased the firing frequency, whereas inhibition of RyRs by 10 microM dantrolene or 80 microm ryanodine decreased firing rate. Similar results were obtained in experiments conducted at either midday or midnight. Furthermore, these effects were not mediated by synaptic transmission as blockade of GABA A, AMPA and NMDA receptors did not prevent the excitatory or inhibitory effects induced by either dose of ryanodine on SCN firing. We conclude that gating of RyRs is a key element of the intricate output pathway from the circadian clock within SCN neurons in rats.

Nicotinic receptor–mediated biphasic effect on neuronal excitability in chick lateral spiriform neurons

Local neuronal circuits integrate synaptic information with different excitatory or inhibitory time windows. Here we report that activation of nicotinic acetylcholine receptors (nAChRs) leads to biphasic effects on excitability in chick lateral spiriform (SPL) neurons during whole cell recordings in brain slices. Carbachol (100 μM in the presence of 1 μM atropine) produced an initial short-term increase in the firing rates of SPL neurons (125±14% of control) that was mediated by postsynaptic nAChRs. However, after 3 min exposure to nicotinic agonists, the firing rate measured during an 800 ms depolarizing pulse declined to 19±7% (100 μM carbachol) or 26±8% (10 μM nicotine) of the control rate and remained decreased for 10–20 min after washout of the agonists. Similarly, after 60 s of electrically-stimulated release of endogenous acetylcholine (ACh) from cholinergic afferent fibers, there was a marked reduction (45±5% of control) in firing rates in SPL neurons. All of these effects were blocked by the nAChR antagonist dihydro-β-erythroidine (30 μM). The inhibitory effect was not observed in Ca 2+-free buffer. The nAChR-mediated inhibition depended on active G-proteins in SPL neurons and was prevented by the GABA B receptor antagonist phaclofen (200 μM), while the GABA B receptor agonist baclofen (10 μM) decreased firing rate in SPL neurons to 13±1% of control. The inhibitory response thus appears to be due to a nAChR-mediated enhancement of presynaptic GABA release, which then activates postsynaptic GABA B receptors. In conclusion, activation of nAChRs in the SPL initiates a limited time window for an excitatory period, after which a prolonged inhibitory effect turns off this window. The prolonged inhibitory effect may serve to protect SPL neurons from excessive excitation.

Spike timing – an incomplete description of neural code

Starting with Hebb's investigations the time domain was an important apparatus to study neuronal activity. Increases or decreases in firing rate, precise spike timing sequences or particular spike time patterns were perceived as the only reliable measures of neural code. Despite considerable efforts and some success, the time approach does not seem to offer responses to several questions. What is the meaning of the time code in terms of behavior? Is the time domain consistent enough to measure complex neuronal activity?

The symptoms of schizophrenia related to the stability of attractor networks

We propose a hypothesis to account for the symptoms of schizophrenia in a statistical dynamical systems framework. We propose that the symptoms of schizophrenia are related to alterations in the depth of the basins of attraction, and the statistical effects of spiking neurons, which together influence the stability of cortical attractor neural networks. The cognitive symptoms such as distractibility, working memory deficits and poor attention could be caused by instability of persistent attractor states in prefrontal cortical networks. The negative symptoms, which include a lack of affect and reduction of emotions, may be related to the concomitant decreased firing rates in cortical areas such as the orbitofrontal cortex and anterior cingulate cortex that occur when the depth of the basins of attraction are reduced. The positive symptoms including delusions, paranoia, and hallucinations could arise because the basins of attraction are shallow in temporal lobe semantic memory networks. This would lead thoughts to move too freely around the attractor energy landscape, loosely from thought to weakly associated thought. These hypotheses were investigated in a model of a cortical attractor network based on integrate-and-fire neurons and synaptic currents activated by AMPA, NMDA and GABA receptors [1]. It was found that a decrease in the NMDA receptor conductance leads to a decrease in the stability of working memory states, an increase in distractibility, and lower firing rates, and can potentially account for both the cognitive and negative symptoms. We observed a flat energy landscape associated with the positive symptoms of schizophrenia when, in addition to a reduction in the NMDA conductance, the GABA conductance was reduced. This caused the dynamical system not only to switch between the high firing rate attractor states, but also sometimes to jump from spontaneous activity into one of the attractor states. The findings are consistent with the neurophysiological effects of dopamine, which can influence NMDA and GABA currents. In this approach we thus start with a statistical dynamical systems framework, and use this to help understand how some of the different symptoms of schizophrenia might arise.

Humidity Detection and Hygropreference Behavior in Larvae of the Tobacco hornworm,Manduca sexta

Water is a critical resource for any terrestrial animal, especially for a soft-bodied insect such as larvae of the tobacco hornworm, Manduca sexta L. (Lepidoptera: Sphingidae). Strategies for coping with a dry environment might include seeking out regions of high relative humidity that reduce desiccative stress, or to find and imbibe liquid water. Desiccated larvae placed in a linear arena with a humidity gradient preferred the humid end, whereas un-desiccated larvae did not. This behavior was not affected by temperature. Ablation or occlusion of the antennae showed that they are required to mediate this behavior. A series of experiments showed that control larvae oriented towards and imbibed liquid water whereas those whose antennae had been occluded with wax did not. Electrophysiological recordings from the lateral basiconic sensillum of the second antennal segment revealed the presence of at least one hygroreceptive unit that greatly increased its firing rate in response to moist air, decreased firing rates in response to dry air, and showed mild post-stimulatory inhibition.

Nonselective cation channels are essential for maintaining intracellular Ca2+ levels and spontaneous firing activity in the midbrain dopamine neurons

Intracellular Ca2+ and Ca2+-permeable ion channels are important in regulating the firing activity and pattern of midbrain dopamine neurons, but the role of Ca2+-permeable nonselective cation channels (NSCCs) on spontaneous firing activity is unclear. Therefore, we investigated how Ca2+-permeable NSCCs modulate spontaneous firing activity and cytosolic Ca2+ concentration ([Ca2+]c) in acutely isolated midbrain dopamine neurons of the rat. Applications of voltage-dependent Ca2+ channels antagonists failed to abolish spontaneous firing activity completely, but they decreased firing rate and [Ca2+]c. However, a blockade of NSCCs by 2-APB or SKF96365 more potently suppressed spontaneous firings with a depolarization of membrane potential and strong decreases in basal [Ca2+]c levels. The depolarization of membrane potentials was attenuated by intracellular dialysis with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). NSCCs blockers inhibited oscillatory potentials and decreased basal [Ca2+]c in the presence of tetrodotoxin. Apamin, a small-conductance Ca2+-activated K+ channel inhibitor, depolarized membrane potentials and enhanced firing rates. From these data, we conclude that NSCCs not only make up the tonic Ca2+ entry pathways to uphold basal [Ca2+]c levels but also contribute to generation of spontaneous firings, thereby regulating spontaneous firing activities of the midbrain dopamine neurons.

Postictal Single‐cell Firing Patterns in the Hippocampus

Patients with epilepsy have varying degrees of postictal impairment including confusion and amnesia. This impairment adds substantially to the disease burden of epilepsy. However, the mechanism responsible for postictal cognitive impairment is unclear. The purpose of this study was to study single-cell firing patterns in hippocampal cells after spontaneous seizures in rats previously subjected to status epilepticus. In this study, we monitored place cells and interneurons in the CA1 region of the hippocampus before and after spontaneous seizures in six epileptic rats with a history of status epilepticus. Place cells fire action potentials when the animal is in a specific location in space, the so-called place field. Place cell function correlates well with performance in tasks of visual-spatial memory and appears to be an excellent surrogate measure of spatial memory. Twelve spontaneous seizures were recorded. After the seizures, a marked decrease in firing rate of action potentials from place cells was noted, whereas interneuron firing was unchanged. In addition, when place cell firing fields persisted or returned, they had aberrant firing fields with reduced coherence and information content. In addition to postictal suppression of firing patterns, seizures led to the emergence of firing fields in previously silent cells, demonstrating a postictal remapping of the hippocampus. These findings demonstrate that postictal alterations in behavior are not due solely to reduced neuronal firing. Rather, the postictal period is characterized by robust and dynamic changes in cell-firing patterns resulting in remapping of the hippocampal map.

Changes in activity of the striatum during formation of a motor habit

To examine experience-dependent plasticity of striatal neurons during habit learning in awake, freely moving animals, single neurons in the dorsolateral striatum (54 neurons related specifically to vertical head movement and 14 unresponsive neurons, i.e. not related to any body movement) were recorded and tracked off-line to assess changes in firing rate over sessions as performance of instrumental head movement became automatic and habitual. Rats were trained to emit operant vertical head movements that triggered water delivery for 14 sessions (2 h per session, one session per day). Rats significantly increased the number and efficiency of head movements over sessions until reaching asymptotic behaviour. Habit formation was indicated by significantly higher levels of instrumental responding exhibited by rats during a late, relative to an early, session in which the reward was devalued. As head movements became habitual across sessions, most head movement-related neurons (89%) exhibited decreased firing rate, while a small population (11%) exhibited increased or maintained firing rate. The rate of decrease in firing by the majority correlated with the rate of improvement in movement efficiency over sessions. All unresponsive neurons, though not apparently related to movement, exhibited decreased firing rate over sessions. Our findings suggest that, during habit learning, the striatum may shift from facilitating acquisition of efficient movement with a large population of neurons to modulating or maintaining habitual movement with stronger firing of fewer movement-related neurons.

Internal Pallidal Neuronal Activity During Mild Drug-Related Dyskinesias in Parkinson's Disease: Decreased Firing Rates and Altered Firing Patterns

The neuronal basis of hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to dyskinesias induced by low doses of apomorphine in patients with advanced Parkinson's disease (PD). During pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of apomorphine at doses just adequate to induce dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with dyskinesias. Among the three neurons in which the onset of on occurred before that of dyskinesias, the firing rate did not change at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias during on with dyskinesias often fluctuated between transient periods with dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with dyskinesias. These results suggest that mild dyskinesias resulting from low doses of apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.

The effects of cirazoline on the firing rates of thermally classified neurons in the anterior hypothalamus of the rat

Peripheral exposure to LPS induces a biphasic fever thought to be initiated via vagal afferents to the anterior hypothalamus (AH), an important thermoregulatory control center in the brain. Previous studies have shown norepinephrine (NE) synaptically mediates this Prostaglandin E2 (PGE2)-dependent change in temperature through the selective activation of α-2 adrenoreceptors (AR). However, there is clear evidence that α-1 AR activation of thermoregulatory hypothalamic neurons will result in a rapid hyperthermia that is not dependent on PGE2. This direct action of NE in the AH was tested in the present study by recording the single-unit activity of these neurons in a tissue slice preparation from the adult male rat, in response to temperature and the selective α-1 AR agonist Cirazoline (10–100 μM). Neurons in the AH were classified as either warm-sensitive (m ≥ 0.8 impulses.s−1.°C−1), or temperature-insensitive. Warm-sensitive neurons responded to cirazoline with a decrease in firing rate, while temperature-insensitive neurons showed an initial firing rate increase. These responses are similar to those reported for PGE2 and suggest that both warm-sensitive and temperature-insensitive neurons in the AH are important in mediating this α-1 AR-dependent hyperthermic shift in body temperature. (Supported by NSF: IBN-9983624, NIH: NS053794 and a HHMI grant to the College of William and Mary.)

Neuronal activity in the primary visual cortex of the cat freely viewing natural images

Many studies have now demonstrated that neurons in the visual cortex of cats and monkeys change their activity when stimuli are presented beyond their classical receptive field, and that these responses are not readily apparent from their receptive field properties. However few studies have been conducted to investigate the discharge properties of neurons in the visual cortex of animals when they are allow to freely view natural images. We employ tetrodes, which enable simultaneous and separable recordings of small numbers of neighboring neurons, to record 102 single units from 59 sites from areas 17 and 18 of two alert cats. While the animals viewed either natural images or black screens, they made frequent saccadic eye movements and gaze fixations. Fixations onto an image’s location increased neuronal firing peaking at 80–100 ms after the fixation onset, to then decrease steadily with time despite continuous fixation. Saccades trigger a fast decrease in firing rate for both images and darkness. When we examined the incidence of correlated firing, we observed significant synchrony during the initial phases of visual fixations when the animals viewed natural scenes. Such synchrony was absent during saccadic eye movements and during eye movements in darkness. Our data revealed that scanning of natural scenes is associated with a rapid succession of distinct fixation-related activation patterns that included transient rate changes and excess coincident firing. The transient nature of these synchronization phenomena suggests a fast acting mechanism, which is in good agreement with the evidence that basic operations of scene analysis must be accomplished within a few tens of milliseconds in primary visual cortex.

Responses of Neurons in the Medial Superior Temporal Visual Area to Apparent Motion Stimuli in Macaque Monkeys

Monkeys fixated a stationary spot during presentation of dot textures that moved in apparent motion defined by the spatial and temporal separations, Deltax and Deltat, between successive flashes of each dot. For each neuron, we assessed the speed tuning for smooth motion (Deltat = 2 or 4 ms) at speeds < or =128 degrees /s and the effect of varying the value of Deltat at speeds of 16 and 32 degrees /s. Many medial superior temporal (MST) neurons, like middle temporal (MT) neurons, were tuned for the speed of smooth motion and showed decreases in firing rate as the value of Deltat increased at a constant speed. A subset of MST neurons, however, showed monotonically increasing firing rates as a function of smooth stimulus speed and responses to apparent motion that paralleled a previously discovered illusion where estimates of target speed increase with the value of Deltat. Opponent firing rate, defined as the difference between responses for motion in the preferred and opposite directions, peaked at values of Deltat that were consistent with the behavioral illusion. Comparison with a new sample of MT neurons recorded with the same stimuli failed to reveal comparable effects. Attempts to map the population responses in MT and MST onto the behavioral illusion of increased speed succeeded by averaging the opponent response across MST neurons, but only by applying vector averaging to determine the preferred speed of the most active MT neurons. We suggest that a vector-averaging computation transforms MT's place code for target speed into the rate code of some MST neurons.

Elevations in local gamma activity are accompanied by changes in the firing rate and information coding capacity of neurons in the region of the subthalamic nucleus in Parkinson's disease

Local field potential (LFP) gamma (55–95 Hz) activity has been recorded in the vicinity of the subthalamic nucleus with both microelectrodes and macroelectrodes in patients with Parkinson's disease undergoing functional neurosurgery. Although this activity increases with movement its functional significance remains unknown. We hypothesised that elevations in local gamma activity might be associated with an increase in the capacity of individual spike trains to code information. Changes in the median firing frequency, entropy and baud were determined during spontaneous variations in the level of simultaneously recorded LFP gamma activity in a sample of 31 neurons. The latter were recorded from the zona incerta ( n = 5) and subthalamic nucleus ( n = 26) in 10 parkinsonian patients. Although 19% of neurons showed a decrease in firing rate, overall there was a net increase in spike frequency and baud of 18.0 ± 5.5% and 16.9 ± 5.3%, when periods of high gamma were compared to periods of low gamma LFP activity. In contrast, entropy dropped by only 0.8 ± 0.2% across the sampled neuronal population during periods of high gamma. All net changes were significant. We conclude that overall there was a net elevation in firing rate and potential information coding capacity, assessed in terms of baud, amongst neurons during periods of elevated gamma LFP activity in the subthalamic region.

Neural Ensemble Coding of Satiety States

The motivation to start or terminate a meal involves the continual updating of information on current body status by central gustatory and reward systems. Previous electrophysiological and neuroimaging investigations revealed region-specific decreases in activity as the subject's state transitions from hunger to satiety. By implanting bundles of microelectrodes in the lateral hypothalamus, orbitofrontal cortex, insular cortex, and amygdala of hungry rats that voluntarily eat to satiety, we have measured the behavior of neuronal populations through the different phases of a complete feeding cycle (hunger-satiety-hunger). Our data show that while most satiety-sensitive units preferentially responded to a unique hunger phase within a cycle, neuronal populations integrated single-unit information in order to reflect the animal's motivational state across the entire cycle, with higher activity levels during the hunger phases. This distributed population code might constitute a neural mechanism underlying meal initiation under different metabolic states.

Deep Brain Stimulation of the Internal Segment of the Globus Pallidus in Delayed Runaway Dyskinesia

Dyskinesias that occur during a period without medication after embryonic cell transplantation have been commonly reported in double-blind trials; however, to date, they have not been reported in the few patients who participated in open-label pilot studies. Single case observation with preoperative and postoperative data, and intraoperative single-cell physiology. A patient who underwent embryonic cell transplantation in 1993 as part of the University of South Florida open-label study was referred for evaluation of intractable dyskinesia of the right arm. The dyskinesia was present during evaluation of the patient after a 12-hour period without medication and was clinically disabling. It was manifested as a severe groping movement of the hand. Intraoperative physiologic evaluation revealed decreased firing rates in the internal segment of the globus pallidus. Deep brain stimulation of the internal segment of the globus pallidus resulted in resolution of the dyskinesia. This case highlights the delayed development of runaway dyskinesia after a period without medication as an important potential long-term adverse effect of embryonic cell transplantation in patients with Parkinson disease.